Question 2: Causal Relationships and Cellular Metabolism Task: Explain the causal chain starting from a gain-of-function mutation in IDH1 or IDH2 to the resulting "differentiation block" observed in leukemic cells. In your answer, specifically address the role of the oncometabolite 2-hydroxyglutarate (2-HG), its effect on the TET family erasers, and how this metabolic shift ultimately prevents stem cells from committing to a specific lineage
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